Nature of the Case and Issue(s) Presented: Spectrum markets Fusilev, a drug composed of levoleucovorin and originally used to treat the side effects of the cancer medicine methotrexate. This indication of the drug was protected by orphan drug exclusivity until March 2015. Spectrum subsequently discovered another use for Fusilev: treating advanced metastatic colorectal cancer. Spectrum also applied for and received orphan drug exclusivity for this colorectal indication until April 29, 2018. The dosage for Fusilev for the colorectal indication is either a large vial dose (150 mg) or a small vial does (15 mg) of the drug, although Spectrum markets Fusilev only in the small vials.

Sandoz also applied for orphan drug protection for the colorectal indication of levoleucovorin in large vials. After Spectrum was granted exclusivity for the colorectal indication, Sandoz amended its application to seek approval to market a generic levoleucovorin product to treat methotrexate toxicity, still in large vial doses, and carved out the use of its product for the colorectal indication. Spectrum submitted a Citizen Petition asking the FDA not to approve ANDAs carving out the colorectal indication in large vial doses and not to approve any generic levoleucovorin products in large vial doses at all. The FDA denied the petition and approved Sandoz’ ANDA. Spectrum then brought this suit, seeking to set aside the FDA’s approval of Sandoz’ generic product, and moved for summary judgement. The court found no reason to overturn the FDA’s decision and denied Spectrum’s motion.

Why Sandoz Prevailed: Spectrum first argued that the FDA’s approval of Sandoz’ ANDA violated the Orphan Drug Act because the FDA knew that the drug would be used for the carved out colorectal indication and because the drug was approved in a form that was only appropriate for the colorectal indication. The court rejected Spectrum’s argument because the Orphan Drug Act is only concerned with the specific FDA approved use—not the use the generic manufacturer may intend. It did not matter that that the FDA might know, or even intend, that doctors would use Sandoz’ generic drug for the colorectal indication. The Orphan Drug Act only prohibits the FDA from approving an application directed to the carved out indication.

Spectrum also argued that the FDA violated its regulations relating to drug shortages when it expedited Sandoz’ ANDA without giving Spectrum notice and opportunity to be heard concerning the shortage of the drug. The court agreed with Spectrum’s argument. The language of the drug shortage regulation, 21 U.S.C. § 316.36, is clear that the FDA was required to give notice to Spectrum if it believed Spectrum would not be able to provide sufficient quantities of the drug. The FDA did not do so. But the court refused to overturn the FDA’s approval because Spectrum did not prove it was prejudiced by the lack of notice. Indeed, on its own volition, Spectrum filed a Citizen Petition with the FDA containing its arguments. Because the FDA then rejected those arguments, the court reasoned that it would be “pointless” to order the FDA to reconsider the same arguments. Accordingly, even if Spectrum had been provided with proper notice, the result would be the same, and no prejudice occurred.

Next, the court rejected Spectrum’s argument that, in approving Sandoz’ ANDA, the FDA reversed its position that the large dose vials of levoleucovorin were only appropriate for the colorectal indication, finding that the FDA never took such a position. When Spectrum applied for orphan drug protection for the colorectal indication, it also filed a supplemental application seeking protection for the large vial dose. While the FDA made statements that the large vials were appropriate for the colorectal indication, and also stated that the methotrexate treatment indication did not require a single dose larger than 50 mg, the FDA never said a larger vial could not be marketed for methotrexate treatment. Further, Spectrum filed a new drug application for large vial ready to use doses listing methotrexate treatment as an application before it granted the exclusivity for colorectal indication. Thus, contrary to Spectrum’s argument, the FDA’s grant to Sandoz’ ANDA was entirely consistent with its past actions.

Finally, Spectrum argued that the FDA’s approval of Sandoz’ ANDA violated FDA regulations that prohibited labelling carve-outs that make generic drugs less safe or effective than the original drug. Spectrum argued that the labelling carve out was unsafe because it increased the risk of vial contamination and overdose. The court rejected disagreed with both points, noting that the same risks existed with Spectrum’s products. Namely, the risk of contamination existed because, after administering a single dose for methotrexate treatment, a portion of the levoleucovorin solution remains as a left over in the vial. Thus, the temptation existed to reuse the remainder, potentially contaminating the drug. Additionally, Spectrum instructs doctors to use multiple small vials to reach the desired dosage. This practice also risks overdose based on a miscalculation. On both points, however, the FDA, based on the rarity of levoleucovorin overdose, had reason to disregard this risk in approving both Spectrum and Sandoz’ products. The court concluded by stating that while “an agency must have reasons for options it chooses, it need not pause to justify every option it does not choose.”

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